The Bacterial Zinc‐Metallophospholipases C

Abstract

The bacterial zinc‐metallophospholipases C are produced only by gram‐positive bacteria and are characterised on the basis of the presence of up to three zinc ions in the active site. Some zinc‐metallophospholipases C, like the α‐toxin of Clostridium perfringens, are potent toxins and play key roles in the pathogenesis of disease. Toxicity appears to be related to the ability of the enzyme to interact with phospholipids in host cell membranes and to the hydrolysis of both phosphatidylcholine and sphingomyelin. Significant insight into the mode of action of the zinc‐metallophospholipases has been gained from knowledge of the crystal structures of several members of this group. All of the enzymes possess an enzymatic domain, but only some zinc‐metallophospholipases possess a domain that can play a key role in the recognition of membrane phospholipids. The presence of this domain appears to be necessary for toxicity, but not all enzymes that possess this domain are toxic. Several studies have indicated that membrane active toxins, such as C. perfringens α‐toxin, might be exploited for the treatment of oncogenic disease.